Bacterial infections in cirrhosis.

Hospitalized patients with cirrhosis are at increased risk of developing bacterial infections, the most common being spontaneous bacterial peritonitis (SBP) and urinary tract infections. Independent predictors of the development of bacterial infections in hospitalized cirrhotic patients are poor liver synthetic function and admission for gastrointestinal hemorrhage. Short term (seven-day) prophylaxis with norfloxacin reduces the rate of infections and improves survival and should therefore be administered to all patients with cirrhosis and variceal hemorrhage. Cirrhotic patients who develop abdominal pain, tenderness, fever, renal failure or hepatic encephalopathy should undergo diagnostic paracentesis, and those who meet the criterion for SBP (eg, an ascites neutrophil count greater than 250/mm3) should receive antibiotics, preferably a third-generation cephalosporin. In addition to antibiotic therapy, albumin infusions have been shown to reduce the risk of renal failure and mortality in patients with SBP, particularly in those with renal dysfunction and hyperbilirubinemia at the time of diagnosis. Patients who recover from an episode of SBP should be given long term prophylaxis with norfloxacin and should be assessed for liver transplantation.     

Bacterial infections in cirrhosis.

Spontaneous bacterial peritonitis, urinary tract infections, respiratory infections and bacteremia are the most frequent infective complications in cirrhosis. These infections are due to the concomitant presence of different facilitating mechanisms including changes in the intestinal flora and in the intestinal barrier, depression of activity of the reticuloendothelial system, decreased opsonic activity of the ascitic fluid, neutrophil leukocyte dysfunction and iatrogenic factors among others. The fact, that the probability of having a microorganism responsible for the infection quinolone resistant is higher than 30% should be taken into account when treating any infection in a cirrhotic patient receiving selective intestinal decontamination with quinolones, and therefore, quinolones as empiric treatment are not indicated.     

Bacterial infections in cirrhosis

Bacterial infections occur in 25–35 % of cirrhotics admitted to hospital. Health-care associated and hospital acquired (nosocomial) infections are the most common epidemiology, with community acquired infections less common (15–30 %). Spontaneous bacterial peritonitis and urinary infections are the most common sites, with spontaneous bacteremia, pneumonia, cellulitis and other sites being less common. The risk of infection is increased among subjects with more severe liver disease and an infection in the past 6 months. Bacteria are isolated from approximately half of patients with a clinical diagnosis of infection. Gram-negative enterobacteriaceae are the most common organisms among community acquired infections; Gram-positive cocci are the most common organisms isolated among subjects with nosocomial infections. Up to 30 % of hospital associated infections are with multidrug resistant bacteria. Consequently, empiric antibiotic therapy that is recommended for community acquired infections is often inadequate for nosocomial infections. Infections worsen liver function. In-hospital and 1-year mortality of cirrhotics with infections is significantly higher than among cirrhotics without infection. In-hospital complications of infections, such as severe sepsis and septic shock, and mortality, are increased among subjects with multidrug-resistant infections as compared with cirrhotics with susceptible bacteria. Short-term antibiotic prophylaxis of cirrhotics with upper gastrointestinal bleeding and long-term antibiotic prophylaxis of selected cirrhotics with spontaneous bacterial peritonitis reduces infections and improves survival. Albumin administration to cirrhotics with SBP and evidence of advanced liver disease improves survival. The benefit of albumin administration to cirrhotics with infections other than SBP is under investigation.     

Bacterial infections in liver cirrhosis

The incidence of bacterial infections in cirrhotic patients admitted to hospital is very high. In several studies, 30% to 50% of cirrhotics presented bacterial infections at admission, or developed this type of complication during hospitalization. Most bacterial infections in cirrhotic patients are hospital-acquired. Between 15% to 35% of cirrhotics admitted to hospital develop nosocomial infections; these figures contrast sharply with the hospital-acquired infection rate in the general hospital population (5% to 7%). Urinary tract infections (12% to 29%), spontaneous bacterial peritonitis (7% to 23%), respiratory tract infections (6% to 10%) and bacteraemia (4% to 9%) are the most frequent bacterial infectious complications seen in cirrhotic patients. However, since spontaneous bacterial peritonitis is the most characteristic bacterial infection in cirrhosis, this report will focus (mainly) on this infectious complication.     

Trimethoprim-sulfamethoxazole versus norfloxacin in the prophylaxis of spontaneous bacterial peritonitis in cirrhosis

BACKGROUND: The prognosis of patients with chronic liver disease and spontaneous bacterial peritonitis is poor, being of great importance its prevention. AIM: To compare the effectiveness of trimethoprim-sulfamethoxazole versus norfloxacin for prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. PATIENTS AND METHODS: Fifty seven patients with cirrhosis and ascites were evaluated between March 1999 and March 2001. All of them had a previous episode of spontaneous bacterial peritonitis or had ascitic fluid protein concentration < or = 1 g/dL and/or serum bilirubin > or = 2.5 mg/dL. The patients were randomly assigned to receive either 800/160 mg/day of trimethoprim-sulfamethoxazole 5 days a week or 400 mg of norfloxacin daily. The mean time of observation was 163 days for the norfloxacin group and 182 days for the trimethoprim-sulfamethoxazole group. In the statistical analysis, differences were considered significant at the level of 0.05. RESULTS: According to the inclusion criteria, 32 patients (56%) were treated with norfloxacin and 25 (44%) with trimethoprim-sulfamethoxazole. Spontaneous bacterial peritonitis occurred in three patients receiving norfloxacin (9.4%) and in four patients receiving trimethoprim-sulfamethoxazole (16.0%). Extraperitoneal infections occurred in 10 patients receiving norfloxacin (31.3%) and in 6 patients receiving trimethoprim-sulfamethoxazole (24.0%). Death occurred in seven patients (21.9%) who received norfloxacin and in five (20.0%) who received trimethoprim-sulfamethoxazole. Side effects occurred only in the trimethoprim-sulfamethoxazole group. CONCLUSION: In spite of the reduced number of patients and time of observation, trimethoprim-sulfamethoxazole and norfloxacin were equally effective in spontaneous bacterial peritonitis prophylaxis, suggesting that trimethoprim-sulfamethoxazole is a valid alternative to norfloxacin.     

Development of quinolone-resistant strains of Escherichia coli in stools of patients with cirrhosis undergoing norfloxacin prophylaxis: clinical consequences.

BACKGROUND/AIM: Norfloxacin prophylaxis decreases the incidence of bacterial infections in high-risk cirrhotic patients, but may promote the development of quinolone-resistant gram-negative bacteria in stools, and eventually lead to infections due to these bacteria. The aim of the study was to evaluate the prevalence of quinolone-resistant strains of E. coli in stools on admission, and the characteristics of any nosocomial infections. METHODS: Eighty-three consecutively hospitalized cirrhotic patients were included in this prospective study. The presence of quinolone-resistant strains of E. coli in stools on admission, and the characteristics of any nosocomial infections were recorded. RESULTS: Fourteen out of 83 patients (16.8%) showed quinolone-resistant E. coli in stools (Group I), and 69 did not (Group II). Thirteen out of 14 from Group I (92.8%) and 17/69 (24.6) from Group II had received primary or secondary prophylaxis with norfloxacin (p<0.001). During hospitalization, 12/12 (100%) of patients from Group I and 25/66 (37.8%) of patients from Group II underwent norfloxacin prophylaxis. Three bacterial infections in patients from Group I, 3 from Group II patients receiving norfloxacin and 16 from Group II patients not receiving norfloxacin were recorded (p<0.05). No infections due to quinolone-resistant E. coli were observed in patients colonized with these bacteria. Treatment with norfloxacin induced the development of quinolone-resistant E. coli in 6/14 (42.8%) patients in a mean time of 18.5+/-9.8 days. CONCLUSIONS: The development of quinolone-resistant strains of E. coli is significantly associated with previous administration of norfloxacin prophylaxis. However, in our series this fact is not associated with an increased incidence of quinolone-resistant E. coli or other gram-negative infections.     

Bacterial infections in cirrhosis: A critical review and practical guidance

Bacterial infection is common and accounts for major morbidity and mortality in cirrhosis. Patients with cirrhosis are immunocompromised and increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. Once infection develops, the excessive response of pro-inflammatory cytokines on a pre-existing hemodynamic dysfunction in cirrhosis further predispose the development of serious complications such as shock, acute-on-chronic liver failure, renal failure, and death. Spontaneous bacterial peritonitis and bacteremia are common in patients with advanced cirrhosis, and are important prognostic landmarks in the natural history of cirrhosis. Notably, the incidence of infections from resistant bacteria has increased significantly in healthcare-associated settings. Serum biomarkers such as procalcitonin may help to improve the diagnosis of bacterial infection. Preventive measures(e.g., avoidance, antibiotic prophylaxis, and vaccination), early recognition, and proper management are required in order to minimize morbidity and mortality of infections in cirrhosis.     

Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies

OBJECTIVE: Patients with hematologic malignancies are at substantial risk of developing invasive fungal infections (IFI) that are associated with substantial morbidity and mortality. This article reviews the epidemiology, risk factors, and efficacy of antifungal prophylaxis in patients with hematologic malignancies. METHODS: A PubMed search was conducted to identify relevant studies with special emphasis on meta-analyses and direct comparisons between antifungal agents. RESULTS: The epidemiology of IFI has changed substantially in recent years with Candida albicans becoming less common owing to the widespread prophylactic use of azole antifungals. Invasive aspergillosis, fusariosis, and zygomycosis have increased in frequency. This change is at least partly related to the use of broad-spectrum antifungal agents, either as prophylaxis or as empirical treatment. Other risk factors for IFI include prior fungal exposure, immunosuppression, underlying disease, graft-vs.-host disease, and organ dysfunction. Inconsistent results have been reported in studies evaluating the efficacy of antifungal prophylaxis in patients at risk of IFI. Meta-analyses found that antifungals, such as fluconazole and itraconazole, are effective in decreasing IFI and IFI-related mortality, primarily owing to yeast infections in patients with more severe immunosuppression (i.e. patients undergoing bone marrow transplantation), but do not decrease the overall mortality. The European Conference on Infections in Leukemia (ECIL) guidelines currently recommend fluconazole (AI, ie. strongly recommended, based on at least 1 well-executed, randomized trial) and itraconazole (BI, ie. generally recommended, based on at least 1 well-executed, randomized trial) in allogeneic transplant recipients. Posaconazole, a triazole antifungal, has been recently shown to decrease IFI incidence and overall mortality in some high-risk patients compared with standard azoles. Based on preliminary data, a provisional AI ECIL recommendation has been given. CONCLUSIONS: Because of the substantial morbidity and mortality associated with IFI, there is a need to accurately define patient groups at greatest risk of IFI and, when appropriate, to initiate effective antifungal prophylaxis.     

Unresolved issues in the prophylaxis of bacterial infections in patients with cirrhosis

Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial infections in high-risk subgroups of patients with cirrhosis has been the standard of care for decades. Patients with prophylaxis indications include those at risk for a first episode of spontaneous bacterial peritonitis(SBP) due to a low ascitic fluid protein count and impaired liver and kidney function, patients with a prior episode of SBP and those with an episode of gastrointestinal bleeding. Only prophylaxis due to gastrointestinal bleeding has a known and short-time duration. All other indications imply longlasting exposure to antibiotics-once the threshold requirement for initiating prophylaxis is met-without standardized criteria for re-assessing antibiotic interruption. Despite the fact that the benefit of antibiotic prophylaxis in reducing bacterial infections episodes and mortality has been thoroughly reported, the extended use of antibiotics in patients with cirrhosis has also had negative consequences, including the emergence of multi-drug resistant bacteria.Currently, it is not clear whether restricting the use of broad and fixed antibiotic regimens, tailoring the choice of antibiotics to local bacterial epidemiology or selecting non-antibiotic strategies will be the preferred antibiotic prophylaxis strategy for patients with cirrhosis in the future.     

Bacterial infections, sepsis, and multiorgan failure in cirrhosis

Bacterial infections are an important complication of cirrhosis, particularly in hospitalized patients. In this article we review the prevalence, risk factors, and pathogenesis of bacterial infections in cirrhosis, focusing on the mechanisms of bacterial translocation such as impaired immunity and bacterial overgrowth, as well as maneuvers that may inhibit bacterial translocation and could be used not only to prevent infections but also to ameliorate the hyperdynamic circulatory state of cirrhosis. We also review the clinical features and management of the most common infection in cirrhosis, spontaneous bacterial peritonitis (SBP), specifically the evidence behind the therapy of acute SBP, the role of albumin, and the role of antibiotics in the prophylaxis of high-risk patients. It has been recognized that SBP and other bacterial infections lead to the systemic inflammatory response syndrome, sepsis, and multiorgan failure. We review the pathogenesis and management of these complications, the role of adrenal insufficiency, and the utility of intensive care prognostic models.     

Bacterial infections other than spontaneous bacterial peritonitis in cirrhosis

Cirrhotic patients are immunocompromised with a high risk of infection.Proinflammatory cytokines and hemodynamic circulation derangement further facilitate the development of serious consequences of infections.Other than spontaneous bacterial peritonitis,bacteremia and bacterial infections of other organ systems are frequently observed.Gram-negative enteric bacteria are the most common causative organism.Other bacterial infections,such as enterococci,Vibrio spp.,Aeromonas spp.,Clostridium spp.,Listeria monocytogenes,Plesiomonas shigelloides and Mycobacterium tuberculosis are more prevalent and more virulent.Generally,intravenous third generation cephalosporins are recommended as empirical antibiotic therapy.Increased incidences of gram-positive and drug-resistant organisms have been reported,particularly in hospitalacquired infections and in patients receiving quinolones prophylaxis.This review focuses upon epidemiology,microbiology,clinical features and treatment of infections in cirrhosis other than spontaneous bacterial peritonitis,including pathogen-specific and liver diseasespecific issues.     

Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage

BACKGROUND & AIMS: Oral norfloxacin is the standard of therapy in the prophylaxis of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. However, during the last years, the epidemiology of bacterial infections in cirrhosis has changed, with a higher incidence of infections caused by quinolone-resistant bacteria. This randomized controlled trial was aimed to compare oral norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection in cirrhotic patients with gastrointestinal bleeding. METHODS: One hundred eleven patients with advanced cirrhosis (at least 2 of the following: ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n = 57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the trial was the prevention of bacterial infections within 10 days after inclusion. RESULTS: Clinical data were comparable between groups. The probability of developing proved or possible infections, proved infections, and spontaneous bacteremia or spontaneous bacterial peritonitis was significantly higher in patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and 12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin), transfusion requirements at inclusion, and failure to control bleeding were independent predictors of infection. Seven gram-negative bacilli were isolated in the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal streptococci were only isolated in the norfloxacin group. No difference in hospital mortality was observed between groups. CONCLUSIONS: Intravenous ceftriaxone is more effective than oral norfloxacin in the prophylaxis of bacterial infections in patients with advanced cirrhosis and hemorrhage.     

Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding

Objective: Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients.
Methods: Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (  n = 28  ) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (  n = 28  ) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission.
Results: Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (   p = NS  ). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (   p = NS  ). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2.
Conclusions: These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.